Efforts have continued on methods to improve the management of high risk thyroid cancer. In one, low dose doxorubicin was used as a radiation enhancer and combined with I-131. Eight patients received 24 such treatments and are being evaluated for potential toxicity. No increased toxicity has been detected thus far. A second method was to give I-131 therapy doses (150 to 300 mCi) to patients with negative diagnostic I-131 scans in whom the presence of cancer was demonstrated by thyroglobulin in blood. In 16 of 17 such patients, post-therapy scans were positive for recurrent or metastatic cancer. The treatment resulted in significant lowering of serum thyroglobulin levels and disappearance of I-131 uptake in lung metastases and other sites. In collaboration with Dr. Ronald Jensen (Livermore National Laboratory and UCSF), the radiation-induced allelic loss of erythrocyte glycophorin A (MN blood type) was used as a biological dosimeter to quantitate radiation to bone marrow in thyroid cancer patients treated with I-131. The results showed an increase in NO and NN variant erythrocytes in proportion to the amount of bone marrow radiation calculated in the conventional manner. Since the effect is cumulative and persistent, it can be used in the evaluation of patients who have received I-131 therapy. In collaboration with Bruce Weintraub, the development of methodology to utilize recombinant human TSH to stimulate I-131 uptake and thyroglobulin release in thyroid cancer is continuing. This will replace the current requirement for patients to become hypothyroid in order to test for residual or recurrent cancer. The multi-institutional Phase III data are now undergoing independent review prior to submission to the FDA for approval.